tbuckley/cabot-search huggingface dataset:
PATH-55. "UNRAVELING THE COMPLEXITIES OF RECURRENT PLEOMORPHIC XANTHOASTROCYTOMA: INSIGHTS FROM ABERRANT IMMUNOHISTOCHEMISTRY AND BRAF V600E MUTATION."
Authors: Marisol Ferrer, Susana Kahl, Belén Nallino, José Nallino, Juan Gil Fauceglia, Jaime Ferrer
Journal: Neuro-Oncology (2023)

Abstract INTRODUCTION Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor that accounts for less than 0.3% of primary central nervous system (CNS) tumors, with an annual incidence of less than 0.7 cases per 100,000 population. PXAs typically express glial fibrillary acidic protein (GFAP), and S100 is often diffusely positive in these tumors. Objetive: To present a long-term multi-recurrence of PXA spanning 12 years which exhibits unusual histological features and an aberrant immunophenotype profile. Patient and methods: We reevaluted the primary tumor, performed a wide panel of immunohistochemistry ( Benchmark Gx Roche) and add molecular testing of BRAFp.V600E mutation and CDKN2 deletion. RESULTS The tumor present fibrillar and epitheliod features in the first recurrence and rhabdoid morphology in the subsequent two resections. All of them were characterized by the absence of GFAP and S100 expression with focal myogenin positivity. This variation in immunohistochemistry adds to the diagnostic challenge in identifying the tumor correctly.The patient's clinical history and the molecular results played a crucial role in defining the diagnosis and guiding treatment decisions. After complete surgical resection the patient received anti-BRAF treatment and has shown an excellent clinical response thus far. CONCLUSIONS This case highlights the extreme pleomorphism of PXA, as evidenced by the unusual histological features and aberrant immunophenotype observed. It emphasizes the diagnostic challenge presented when morphological and immunohistochemical characteristics deviate from the usual pattern. Molecular biology techniques, including genetic testing, are crucial in such cases to aid in accurate diagnosis, guide treatment decisions, and improve patient outcomes.
EXTH-34. LOCAL DELIVERY OF AN IL-15 SUPERAGONIST USING A REPLICATING RETROVIRUS SYNGERIZES WITH TEMOZOLOMIDE TO INCREASE LYMPHOCYTE INFILTRATION AND SURVIVAL IN TWO POORLY IMMUNOGENIC GLIOBLASTOMA MOUSE MODELS
Authors: Alexander F Haddad, Jordan Spatz, Atul Saha, Megan Montoya, Sara Collins, Sabraj Gill, Elaina Wang, Pavlina Chuntova, Diana Salha, Jacob Young, Noriyuki Kasahara, Manish Aghi
Journal: Neuro-Oncology (2023)

Abstract Glioblastoma (GBM) leads to systemic and local immunosuppression and immunotherapies have had limited clinical success. We evaluated the treatment efficacy of RLI (receptor-linker-IL-15), a superagonist of T-cell activator IL-15, delivered to tumor cells using a tumor-selective retroviral replicating vector (RRV) in the syngeneic murine SB28 and Tu2449 GBM models, which are poorly immunogenic with low-mutational burden and known resistance to immunotherapy, similar to human GBM. RRV-RLI replicated and spread in cultured SB28 murine GBM cells with robust production of functional RLI (165.4 ± 5.3 ng/mL). Stereotactic injection of RRV-RLI into pre-established intracerebral Tu2449 tumors led to complete eradication of intracerebral tumors with long term survival (median not reached) in &amp;gt; 85% of treated mice vs. median survival of 12.5 days in control mice (p=0.001). Treated mice demonstrated significantly increased CD8 T cell infiltration. These mice also demonstrated immunologic memory to intracranial rechallenge. In SB28, RRV-RLI delivery into intracerebral tumors reduced tumor growth on bioluminescence imaging, and increased median survival compared to controls (55 vs. 19 days, p=0.002), with long-term survival in 12% of treated mice. Combining RRV-RLI treatment with systemically administered temozolomide (TMZ) in the SB28 model provided long term survival (median not reached) in &amp;gt;60% of treated mice. Immunologic analysis of treated tumors revealed a significant increase in CD8 T cell (2.1% to 20.5% of CD45 cells) and Natural Killer cell (1.4% to 9.6% of CD45 cells )infiltration in RLI-RRV+TMZ mice vs. PBS+TMZ mice. RLI was not detected in the blood of treated mice, and tumor-localized RRV-RLI gene delivery showed no adverse systemic immune effects. In summary, RRV-mediated RLI immunotherapy results in immunostimulatory changes that are further potentiated by systemically administered temozolomide. This tumor-localized gene therapy has the potential to synergize with standard of care treatment to reverse the immunosuppressed GBM tumor microenvironment and provide a significant treatment benefit.
NCOG-01. BASELINE PATIENT-REPORTED OUTCOMES IN AN ONGOING PHASE III TRIAL OF PRE-OPERATIVE SRS VERSUS POST-OPERATIVE SRS FOR BRAIN METASTASES
Authors: Mariana Bradshaw, Jeffrey Wefel, Kyle Noll, Ganesh Rao, Sherise Ferguson, Hussein Tawbi, Jason Huse, Jason Johnson, Laurence Court, Barbara O'Brien, Frederick Lang, Lynette Ejezie, Catherine Sullaway, Ashley Thomas, Dima Suki, D Nana Yeboa
Journal: Neuro-Oncology (2023)

Abstract In ongoing phase III randomized trial (NCT03741673) evaluating risk of LMD in patients with brain metastasis, patients are stratified by tumor size, location, and histology, and randomized to pre- versus post-operative SRS. Exploratory endpoints include patient reported outcomes (PROs) assessing symptoms (MDASI-BT) and health status (EQ-5D-5L). Characteristics of patients (N=40) with pre-treatment baseline include: mean (SD): age 59.3(11.4) years; 2.6(2.2) mets; 15.2(10.3) cc brain met volume; median KPS: 90 (range: 70-100). On the MDASI-BT, 22.5%, 47.5%, 27.5%, 12.5%, and 80% reported no symptoms on the Cognitive, Neurologic, Affective, Constitutional, and Gastrointestinal Factors, respectively. The median factor score was &amp;lt;1 on all factors. Neurologic (r=-.35, p=.03) and Constitutional Factors (r=-0.34, p=.03) correlated with KPS. There was no correlation between MDASI-BT Factors and number/volume of metastases. On the EQ-5D-5L, patients reported no problems with Mobility (45%), Self-Care (72.5%), Usual Activities (62.5%), Pain/Discomfort (55%), and Anxiety/Depression (52.5%). Nearly twenty-eight percent reported no problems in any domain. KPS correlated with Mobility (r=-.48, p&amp;lt; 0.01), Self-Care (r=-.49, p&amp;lt; 0.01), and Usual Activities (r=-.44, p&amp;lt; 0.01). There was no association between EQ-5D-5L items and number/volume of metastases. Patients’ baseline rating of current health on a 0-100 scale (VAS) ranged from 30-100 (mean (SD)=72.25 (19.18)). VAS correlated most with Anxiety/Depression (r=-.40, p=.01). VAS also correlated significantly with MDASI-BT Affective Factor (r=-.541, p&amp;lt; .001) but not with Cognitive or Neurologic Factors. There was no correlation between VAS and KPS or number/volume of metastases. As previously reported, objective measures of cognitive function are associated with disease characteristics. PROs were associated with performance status but not disease characteristics. Mood was more strongly associated with patients’ self-perception of overall health status than clinical or disease characteristics. At baseline, a high proportion of patients report no adverse symptoms, suggesting use of these outcomes is best suited to trials measuring worsening of symptoms.
NIMG-78. USE OF ARTERIAL SPIN LABELING TO DETECT METASTASIS OF MENINGEAL SOLITARY FIBROUS TUMORS
Authors: Katelyn Costanza, Alp Oztek, Jalal Andre, Tresa McGranahan
Journal: Neuro-Oncology (2023)

Abstract Meningeal solitary fibrous tumors (SFT), formerly known as hemangiopericytoma, are rare, highly vascular, mesenchymal dural based neoplasms. Meningeal SFT require lifelong imaging surveillance given high risk of recurrence and metastasis, even decades after initial diagnosis. Often these metastases are initially small, nodular dural masses that are difficult to detect with standard brain tumor imaging protocols. Given SFT are highly vascular tumors, we hypothesized that recurrent meningeal SFT would have elevated cerebral blood flow using Arterial Spin Labeling (ASL) perfusion imaging. ASL is a noninvasive MRI technique used to detect cerebral blood flow in high grade neoplasms and hyper vascular meningiomas without intravenous contrast. We evaluated ASL in two patients with recurrent meningeal SFT. In both patients the recurrent meningeal SFT demonstrated elevated perfusion by ASL. In one patient, the elevated ASL signature enabled identification of a small metastasis that was not initially appreciated on structural imaging. Following treatment with antiangiogenic therapy, ASL was no longer elevated while enhancement did not change. To our knowledge, this is the first study reporting utility of ASL imaging in detecting intracranial recurrence of meningeal SFT. We propose further study of sensitivity of ASL to detect recurrent meningeal SFT.
NIMG-31. AXONS INTERSECTING TUMOR ENHANCEMENT (AXITE) RADIOMICS: A NOVEL PREDICTOR FOR OVERALL SURVIVAL IN GLIOBLASTOMA
Authors: Biprojit Nath, Aleksandra Winiarz, Samuel Bobholz, Allison Lowman, Savannah Duenweg, Margaret Stebbins, Michael Flatley, Fitzgerald Kyereme, Jennifer Connelly, Dylan Coss, Max Krucoff, Anjishnu Banerjee, Peter LaViolette
Journal: Neuro-Oncology (2023)

Abstract AIM The diffuse infiltration of glioblastoma (GBM) along the intricate network of white matter (WM) tracts poses a major challenge. Our aim is to investigate the potential of axons intersecting tumor enhancement (AXITE)-derived radiomic features in predicting one-year overall survival (OS), in comparison to conventional tumor-based radiomics. METHODS This study included data from the publicly available UCSF-PDGM-v2 (n=97). T1+C images and their corresponding tumor mask were rigidly registered to a common brain template (MNI152) using ANTs. WM tracts within the tumor-defined region of interest were generated using the HCP1065-1mm tractography atlas in DSI Studio Software, which mapped the AXITEs. Radiomic features were then extracted using PyRadiomics from subsequently masked AXITE maps as well as contrast-enhancing tumor masks for a comparative analysis. Four machine learning models, including a Random Forest, Support Vector Machine (SVM), Decision Tree, and Logistic Regression, were employed to predict OS using an 80/20 train/test split. RESULTS Among all models, SVM was the most effective in predicting OS. AXITE radiomics demonstrated remarkable precision (0.73 for OS &amp;lt; 1 yr and 0.78 for OS &amp;gt;1yr), accuracy (0.75), F1-Score (0.75), recall (0.75), and AUC of 0.84 in ROC analysis outclassing the performance of traditional tumor radiomics which had an accuracy (0.60), precision (0.66), F1-Score (0.56) and AUC of 0.60. CONCLUSIONS AXITE Radiomics holds promising potential in capturing tumoral heterogeneity and white matter tract infiltration of GBM, demonstrating superior prediction over traditional tumor radiomics. Our approach presents a more accurate representation of tumor invasiveness and tumor resistance associated with OS more accurately and promises a potential tool for improving patient prognosis and patient management.
NIMG-75. POSTOPERATIVE68GA-DOTATATE/PET-CT IMAGING IS PROGNOSTIC FOR PROGRESSION-FREE SURVIVAL IN MENINGIOMA WHO GRADE 1: A PROSPECTIVE SINGLE-CENTER STUDY
Authors: Nico Teske, Annamaria Biczok, Stefanie Quach, Franziska J Dekorsy, Robert Forbrig, Raphael Bodensohn, Maximilian Niyazi, Joerg-Christian Tonn, Nathalie Albert, Christian Schichor, Moritz Ueberschaer
Journal: Neuro-Oncology (2023)

Abstract PURPOSE Microsurgical tumor resection represents the first-line treatment for symptomatic meningiomas, and extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. However, prognostic relevance of postoperative PET for progression-free survival in meningiomas remains unclear. METHODS We conducted a prospective study including patients with surgically removed meningioma WHO grade 1 and collected clinical and imaging data. All patients received postoperative MRI and 68Gallium-DOTATATE/PET, and were followed regularly with MRI surveillance scans for detection of tumor recurrence/progression. RESULTS We included 46 patients with 49 tumors. Mean age at diagnosis was 57.8 ± 1.7 years with a male-to-female ratio of 1:1.7. Local tumor progression occurred in 7/49 patients (14%) after a median follow-up of 52 months. Positive PET was associated with an increased risk for progression (*p = 0.015) and a lower progression-free survival (*p = 0.029) whereas MRI was not. 20/20 patients (100%) with negative PET findings remained recurrence-free. Location of recurrence/progression on MRI was adjacent to regions where postoperative PET indicated tumor remnants in all cases. Gross tumor volumes were higher on PET compared to MRI (*p = 0.032). CONCLUSION Our data show that 68Ga-DOTATATE/PET is highly sensitive in revealing tumor remnants in patients with meningioma WHO grade 1. Negative PET findings were associated with a higher progression-free survival, thus improving surveillance. In patients with tumor remnants, additional PET can optimize adjuvant radiotherapy target planning of surgically resected meningiomas.
NCOG-03. SURGICAL MANAGEMENT OF CRANIOSPINAL AXIS MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A SINGLE-INSTITUTION EXPERIENCE AND LITERATURE REVIEW
Authors: A J Chowdhury, Juan Vivanco-Suarez, Alex Belzer, Nahom Teferi, Patrick Hitchon
Journal: Neuro-Oncology (2023)

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are exceedingly rare and aggressive tumors with an overall incidence rate of 0.001%. The craniospinal axis is a rare location for primary MPNSTs with very few cases reported in the literature to date. Here-in, we present one of the larger series of single-institutional primary craniospinal MPNSTs, analyze patient outcomes, and extensively review the associated literature. All primary craniospinal axis MPNSTs managed at our institution between January 2005 to May 2023 were retrospectively reviewed. Patient demographics, tumor characteristics and radiographic features, treatment, and clinical outcomes were collected and analyzed. Descriptive statistics and multivariate logistic regression were performed. A total of 8 patients satisfied inclusion criteria (4 male and 4 female patients). Median age at presentation was 40 years (range 34-80 years). Most of these tumors were localized to the spine (6, 75%) and 3 patients (37%) had neurofibromatosis type 1(NF-1). Most common presenting symptoms were paresthesia/numbness in 50% of cases, and vision changes in 13%. Median tumor size was 3 cm (range 1-20), and most tumors were oval-shaped (4, 50%), with well-defined borders (6, 75%). One spinal tumor (11%) had an intramedullary extension. Most tumors were high grade (6, 75%), and gross-total resection was achieved in 5 (63%) patients with subtotal resection performed in the remaining 3 (37%). Radiotherapy and chemotherapy after surgery were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence was evidenced in 5 (63%) cases and distant metastatic disease in 2 (25%) cases. The median progression-free survival time was 26.0 months, and 5 (63%) patients died due to recurrent disease. Early diagnosis and initiation of treatment is key as these tumors are highly aggressive with increased local invasion and distant metastatic rates. Maximal safe gross total resection with negative margins with adjuvant radiation therapy is associated with improved survival.
EXTH-32. SYNERGISTIC EFFICACY OF Y BOX BINDING PROTEIN 1 (YBX1) INHIBITION COMBINED WITH CHEMOTHERAPY FOR THE TREATMENT OF <i>MYC</i>-AMPLIFIED MEDULLOBLASTOMA
Authors: Stephen Carney, Christian Bonatto, Guadalupe Guadarrama, Dhanir Tailor, Sanjay Malhotra, Myron Evans
Journal: Neuro-Oncology (2023)

Abstract Medulloblastoma is the most common pediatric brain tumor in children. Patients diagnosed with MYC-amplified group 3 (G3) have a dismal prognosis with a 5 year survival rate of &amp;lt; 50%. Standard of care consists of maximal resection surgery followed by craniospinal irradiation and chemotherapy, but patients experience diminished quality of life from these extensive treatment regimens. Recent observations have shown that Y-box binding protein 1 (YBX1) is upregulated across human medulloblastoma subgroups compared to normal cerebellum. G3 patient tumors have the highest expression of YBX1, possibly due to an oncogenic feedback loop. We utilized an orthogonal pharmacogenetic approach to target YBX1. Knockdown/out of YBX1 significantly inhibits proliferation of G3 MB cells in vitro and in vivo. We next investigated the therapeutic potential of a novel YBX1 inhibitor, which displays single agent efficacy at decreasing the proliferation of medulloblastoma cell line derived xenografts (CDX). Since YBX1 targeting downregulated ABC transporter expression, we hypothesize that inhibition of YBX1 may sensitize medulloblastoma cells to chemotherapeutic agents. We performed drug synergy experiments combining YBX1 inhibition and commonly used standard of care chemotherapy. We identify that combining YBX1 inhibition sensitizes to both gemcitabine and vincristine in vitro and in vivo. We are currently evaluating this YBX1 inhibitor in an “anchor-probe” screen combining with all currently FDA approved drugs. Our findings impart an alluring prospect of targeting YBX1 in combination with chemotherapy, and possibly other compounds could improve patients’ outcomes.
NIMG-76. A DEEP LEARNING ALGORITHM FOR FULLY AUTOMATED VOLUMETRIC MEASUREMENT OF MENINGIOMA BURDEN
Authors: Mason Cleveland, Albert Kim, Jay Patel, Owen McCall, William Liu, Syed Ahmed, Benjamin Bearce, Ken Chang, Magali De Sauvage, Katharina Hoebel, Juliana Larson, Naema Nayyar, Dagoberto Pulido, Praveer Singh, Elizabeth Summers, Jayashree Kalpathy-Cramer, Scott R Plotkin, Priscilla Brastianos, Christopher Bridge, Elizabeth Gerstner
Journal: Neuro-Oncology (2023)

Abstract PURPOSE Meningiomas are the most common primary central nervous system tumor. A subset of these tumors is multiply recurrent despite aggressive treatment with surgery or radiation and causes significant morbidity and mortality. Longitudinal measurement of meningioma burden on post-contrast MRI is the basis of treatment response assessment. As per Response Assessment in Neuro-Oncology (RANO), estimates of tumor size are based on the product of bidirectional diameters of enhancing tumor. However, these 2D segmentations as well as manual volumetric segmentations have high rates of intra- and inter-rater variability, which prohibits accurate longitudinal assessment of tumor size. A rapid and reproducible quantitative method for determining meningioma volume is needed to expedite response assessment in clinical trials. To address this unmet need, we developed a deep learning algorithm that enables fully automated 3D segmentation and volumetric assessment of meningioma burden. METHODS 351 post-contrast T1-weighted brain MRIs from 86 patients with meningioma were obtained from Massachusetts General Hospital and Dana-Farber Cancer Institute. The cohort was unique compared to prior DL segmentation models as it encompassed diverse clinical scenarios (e.g., meningioma of all grades, post-operative and post-radiated meningioma). The MRIs were resampled to 1 mm isotropic resolution and preprocessed using N4 bias field correction and zero-mean intensity normalization. The dataset was split 70%/15%/15% for training/validation/testing on a per patient level. The training data were used with manually generated tumor segmentations to train a convolutional neural network (CNN) with a U-Net architecture and the Dice loss function. RESULTS The median Dice score was 0.6758 on the test set. Additional work is ongoing to optimize performance, with primary focus directed toward improved data preprocessing and ground truth segmentation as the variability in segmentation quality contributed to the lower Dice score, highlighting the need to develop a less biased and more reliable tool to segment meningiomas.
EXTH-33. RAGE INHIBITOR (TTP488) AS AN ALTERNATIVE TO DEXAMETHASONE FOR MANAGING CEREBRAL EDEMA FOLLOWING BRAIN TUMOR SURGERY
Authors: Mojtaba Dayyani, Aleksandr Filippov, Ian Zhang, Joseph Georges, Zaan Saeed, Jillyn Turunen, Larry Zhang, Rachel Maus, Jana Portnow, Behnam Badie
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Cerebral edema (CE) commonly occurs after neurosurgical procedures and contributes to patient morbidity and neurological deterioration. Corticosteroids alleviate brain edema during the perioperative period, but they impose several undesirable side effects and interfere with immunotherapies in patients with malignant brain tumors. OBJECTIVE To assess the anti-inflammatory effects of TTP488 (inhibitor of receptor for advanced glycation end products) on CE formation following tumor resection in glioma models. METHODS Mice harboring orthotopic CT-2A gliomas were randomly assigned to three groups and underwent tumor resection. TTP488, dexamethasone, and vehicle were administered perioperatively (day -4 pre-op to day 7 post-op) and post-operative neurological function was examined. CE was assessed on serial brain MRIs over a 7-day period, and using manual segmentation techniques, tumor-related volumes were calculated. In a separate survival experiment, the effect of each drug on anti-PD-1 immunotherapy response was measured. RESULTS In each group, CE peaked on post-operative day 2 and gradually diminished by day 7. On post-operative day one, mice treated with TTP488 showed a marked reduction in CE compared to those treated with either dexamethasone or vehicle with mean CE volumes of 1.75±1.08%, 2.69±0.77%, and 3.87±1.07%, respectively (P=0.02, TTP488 vs vehicle). Furthermore, the TTP488 group had better functional recovery scores (P=0.04) and wound healing (dehiscence, P=0.00003) compared to the vehicle group. Interestingly, unlike dexamethasone, TTP488 did not abrogate the efficacy of immunotherapy in the CT-2A glioma model. CONCLUSION TTP488 was as effective as dexamethasone in alleviating CE caused by tumor resection and did not interfere with the efficacy of immunotherapy. TTP488 could potentially be an alternative to dexamethasone in the perioperative management of patients undergoing tumor resection or other neurosurgical interventions.